Methods to optimize myxobacterial fermentations using off-gas analysis

Hüttel Stephan, Muller, Rolf Muller

Description

The influence of carbon dioxide and oxygen on microbial secondary metabolite producers and the maintenance of these two parameters at optimal levels have been studied extensively. Nevertheless, most studies have focussed on their influence on specific product formation and condition optimization of established processes. Considerably less attention has been paid to the influence of reduced or elevated carbon dioxide and oxygen levels on the overall metabolite profiles of the investigated organisms. The synergistic action of both gases has garnered even less attention. Results We show that the composition of the gas phase is highly important for the production of different metabolites and present a simple approach that enables the maintenance of defined concentrations of both O 2 and CO 2 during bioprocesses over broad concentration ranges with a minimal instrumental setup by using endogenously produced CO 2 . The metabolite profiles of a myxobacterium belonging to the genus Chondromyces grown under various concentrations of CO 2 and O 2 showed considerable differences. Production of two unknown, highly cytotoxic compounds and one antimicrobial substance was found to increase depending on the gas composition. In addition, the observation of CO 2 and O 2 in the exhaust gas allowed optimization and control of production processes. Conclusions Myxobacteria are becoming increasingly important due to their potential for bioactive secondary metabolite production. Our studies show that the influence of different gas partial pressures should not be underestimated during screening processes for novel compounds and that our described method provides a simple tool to investigate this question.

Sujets

• Myxobacteria
• Secondary metabolite
• Carbon dioxide
• Oxygen
• Business process automation
• Bioprocess
• Coq
• Po2

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 15
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Hüttel and MüllerMicrobial Cell Factories2012,11:59 http://www.microbialcellfactories.com/content/11/1/59

R E S E A R C H

Methods to optimize myxobacterial using offgas analysis 1 1,2* Stephan Hüttel and Rolf Müller

Open Access

fermentations

Abstract Background:The influence of carbon dioxide and oxygen on microbial secondary metabolite producers and the maintenance of these two parameters at optimal levels have been studied extensively. Nevertheless, most studies have focussed on their influence on specific product formation and condition optimization of established processes. Considerably less attention has been paid to the influence of reduced or elevated carbon dioxide and oxygen levels on the overall metabolite profiles of the investigated organisms. The synergistic action of both gases has garnered even less attention. Results:We show that the composition of the gas phase is highly important for the production of different metabolites and present a simple approach that enables the maintenance of defined concentrations of both O 2 and CO 2 during bioprocesses over broad concentration ranges with a minimal instrumental setup by using endogenously produced CO 2 . The metabolite profiles of a myxobacterium belonging to the genusChondromyces grown under various concentrations of CO 2 and O 2 showed considerable differences. Production of two unknown, highly cytotoxic compounds and one antimicrobial substance was found to increase depending on the gas composition. In addition, the observation of CO 2 and O 2 in the exhaust gas allowed optimization and control of production processes. Conclusions:Myxobacteria are becoming increasingly important due to their potential for bioactive secondary metabolite production. Our studies show that the influence of different gas partial pressures should not be underestimated during screening processes for novel compounds and that our described method provides a simple tool to investigate this question. Keywords:Myxobacteria, Secondary metabolites, Carbon dioxide, Oxygen, Process automation, Production optimization, Bioprocess, OCQ, COQ, pO 2 , pCO 2

Background The search for new antibiotics and other bioactive com pounds has been intensified due to the development of multiple resistances in pathogenic bacteria and the lack of effective therapies against various  not only infectious diseases [1,2]. Despite welldeveloped techniques to create synthetic compound libraries, the chemical variety and complexity found in natural molecules are often inaccess ible via synthesis and lead structures from Nature are still in demand [3]. Bacteria are welldocumented sources for these

* Correspondence: [e-mail]aarland.de 1 Department of Pharmaceutical Biotechnology, Saarland University, Saarbruecken, Germany 2 HelmholtzInstitute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology Saarland University, Saarbruecken, Germany

desired structures and, among microbes, myxobacteria are an important group, responsible for approximately 5% of the known bacterial compounds including molecules of considerable pharmaceutical interest [4,5]. Although thou sands of different myxobacteria from diverse environmental sources have already been isolated and new species and even genera are still discovered [6], little is known about bioprocesses involving myxobacteria. The myxobacterial genusChondromycesappears to be a promising source for novel structures as several bioactive molecules, such as the chondramides and apicularens, have already been isolated and characterized [7,8]. To investigate the influence of the gaseous composition on myxobacterial growth and metabolic profile, SBCm007, aChondromyces strain isolated in our laboratory, was chosen for its produc tion of several uncharacterized compounds in addition to

© 2012 Hüttel and Müller; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.